Progressive Axonopathy: An Inherited Neuropathy of Boxer Dogs. 2. The Nature and Distribution of the Pathological Changes

Abstract

This report describes the neuropathology of progressive axonopathy (PA), an autosomal recessive inherited neuropathy of Boxer dogs, which affects CNS and PNS. The nerve roots contain numerous myelin bubbles and proximal paranodal axonal swellings containing vesicles, vesiculo-tubular profiles and disorganized neurofilaments. The myelin sheath overlying such swellings is often attenuated. As the disease develops there are progressive changes in the myelin sheath with thinning at paranodal and internodal locations, loss of myelin from lengths of axon and the formation of short internodes with disproportionately thin sheaths. The abnormalities show a very definite selectivity for nerve roots and proximal nerves. Conversely, the frequency of degeneration and regeneration is greater distally except in the cervical ventral roots which contain numerous regenerating clusters. In the CNS numerous axonal spheroids are found in the lateral and ventral columns of the spinal cord and in various brain stem nuclei, particularly the superior olives, accessory cuneate nuclei and lateral lemniscus and its nucleus. Axonal degeneration which occurs mainly in the cord shows no obvious tract or proximal/distal selectivity. The optic pathways are also involved, predominantly adjacent to the chiasma. The autonomic nervous system is affected and distal limb muscles show varying, but usually minor, degrees of neurogenic atrophy. The condition, which has no obvious direct parallel in human or veterinary medicine, shows gross disturbances of axon-glial inter-relationships in both CNS and PNS.

Degenerative Myelopathy in Two Boxer Dogs

“…6 Affected dogs manifest signs at an early age and progress rapidly, in contrast to the late onset, slowly progressive clinical course of DM. 6 The spheroids in progressive axonopathy are conspicuously absent in DM, suggesting a different pathogenesis. Indeed, the spheroids contain large accumulations of neurofilaments and therefore could reflect a form of neuraxonal dystrophy in which normal neuronal transport is inhibited.…”

“…Indeed, the spheroids contain large accumulations of neurofilaments and therefore could reflect a form of neuraxonal dystrophy in which normal neuronal transport is inhibited. 6 The lack of inflammation in cases of DM suggests that the loss of myelin and damage to the axon is not a direct effect of an infectious agent but is rather a failure of maintenance of the continuity of the myelin sheath, of normal axon function, or both. As such, several hypotheses have been examined as to the cause of the degenerative changes in the spinal cord; however, the underlying pathophysiology remains unclear.…”

“…6 In this disease, numerous axonal spheroids develop in the spinal cord and brain stem nuclei in concurrence with degeneration of the lateral and ventral funiculi of the spinal cord. 6 Affected dogs manifest signs at an early age and progress rapidly, in contrast to the late onset, slowly progressive clinical course of DM. 6 The spheroids in progressive axonopathy are conspicuously absent in DM, suggesting a different pathogenesis.…”

Tetraparesis, Hemiparesis, and Ataxia

“…Lesion distributions are variable. Central-peripheral axonopathy of young dogs have been described in the Ibizan hound, 149 Alaskan husky, 183 boxer, [184][185][186] Pyrenean mountain dog, 187 and New Zealand Huntaway. 175 Breeds described include Jack Russell and smooth fox terriers, [176][177][178] Scottish terrier, 179 and Labrador retriever.…”

Progressive Axonopathy: An Inherited Neuropathy of Boxer Dogs. An Immunocytochemical Study of the Axonal Cytoskeleton

“…Progressive axonopathy is an inherited neuropathy affecting the central (CNS) and peripheral (PNS) nervous system of boxer dogs. The pathological changes have been described in detail (Griffiths, McCulloch & Abrahams, 1985, 1986, 1987. The disease is characterized by axonal spheroids in the white matter of the spinal cord, in specific brain stem nuclei and in nerve Correspondence to: I. R. Griffiths, Department Veterinary Surgery, University of Glasgow Veterinary School, Bearsden Road, Glasgow G61 1QH roots.…”